ras, rab and rho/rac are small membrane-bound GTPases that function as key control switches in mitogenic signal transduction, membrane trafficking and cytoskeletal organization, respectively. Oncogenic mutants of ras genes are the transforming genes most frequently found in human cancers and ras has been one of the most intensively studied proteins of the past decade. It is now becoming clear that an expanding menagerie of other proteins interact with ras and influence its GTPase and guanine nucleotide exchange activities. For ras to function (or mal-function as the case may be), it must be located at its site of action on the inner surface of the plasma membrane. ras is targeted to and anchored to the membrane by virtue of an isoprenoid lipid group that is post-translationally attached to ras by a heterodimeric enzyme called farnesyltransferase (FTase). Other ras-like proteins are modified by geranylgeranylation (type I and II enzymes). Inhibitors of FTase have recently been developed and show considerable promise as a new class of anticancer drugs. Through database searching and multiple sequence alignment, we have identified highly-conserved domains and sequence motifs in GTPase-activating proteins (GAP), guanine nucleotide-releasing proteins (GNRP), guanine nucleotide dissociation inhibitors (GDI), and prenyltransferase subunits. We discovered pleckstrin homology (PH) domains in p120 rasGAP and rasGNRP. Sequence homologies between the human choroideremia gene product, rabGDI and the yeast protein Mrs6 were identified and characterized and the latter inferred to be "rab escort protein" that forms the third subunit of type II geranylgeranyltransferase.